5-132715864-C-A

Variant names:

• chr5-132715864-C-A
• rs754855003
• NM_001300791.2:c.1022G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001300791.2(KIF3A):​c.1022G>T​(p.Arg341Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R341H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KIF3A NM_001300791.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

KIF3A (HGNC:6319): (kinesin family member 3A) Enables protein phosphatase binding activity; small GTPase binding activity; and spectrin binding activity. Involved in protein localization to cell junction and protein transport. Located in centriole and centrosome. Part of kinesin II complex. Colocalizes with spindle microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000230612 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300791.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF3A	NM_001300791.2	MANE Select	c.1022G>T	p.Arg341Leu	missense	Exon 8 of 19	NP_001287720.1	E9PES4
	KIF3A	NM_001300792.2		c.1022G>T	p.Arg341Leu	missense	Exon 8 of 18	NP_001287721.1	J3KPF9
	KIF3A	NM_007054.7		c.1022G>T	p.Arg341Leu	missense	Exon 8 of 17	NP_008985.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF3A	ENST00000403231.6	TSL:2 MANE Select	c.1022G>T	p.Arg341Leu	missense	Exon 8 of 19	ENSP00000385808.1	E9PES4
	KIF3A	ENST00000378735.5	TSL:1	c.1022G>T	p.Arg341Leu	missense	Exon 8 of 18	ENSP00000368009.1	J3KPF9
	KIF3A	ENST00000618515.4	TSL:5	c.1022G>T	p.Arg341Leu	missense	Exon 8 of 19	ENSP00000483023.1	A0A087X011

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457110 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725146

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.00 AC: 0 AN: 85920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108412

Other (OTH) AF: 0.00 AC: 0 AN: 60200

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.85	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.96
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-6.4	D
REVEL	Pathogenic	0.91
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.76		Loss of MoRF binding (P = 0.0269)
MVP		0.84
MPC		1.9
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.89
gMVP		0.79
Mutation Taster		=20/80	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs754855003; hg19: chr5-132051556;